Osmotically driven active agent delivery device providing an ascending release profile

Abstract

In one aspect, the present invention is directed to an osmotic pump that automatically provides an ascending release rate of active agent as the osmotic pump functions in an environment of operation and may be designed for implantation within a desired animal or human subject. An osmotic pump according to the present invention includes a reservoir, a rate controlling membrane, an expandable osmotic composition, an active agent formulation and an exit orifice. Once administered to an environment of operation, water passes through the rate controlling membrane and into the osmotic composition, which causes the osmotic composition to expand and expel the active agent formulation through the exit orifice at a rate that is directly proportional to the rate at which water passes through the rate controlling membrane. An osmotic pump according to the present invention permits the flow of water through the rate controlling membrane to increase automatically without the need for manipulation of the osmotic pump after administration. As the flow of water through the rate controlling membrane increases, the rate at which active agent is delivered from the osmotic pump will also increase proportionally.

1. An osmotic pump that automatically provides an ascending release rate of active agent comprising:
 a reservoir having an opening at a first end and a delivery orifice at a second end; 
 a rate controlling member coupled to the first end of the reservoir, wherein the rate controlling member comprises a semipermeable material having a substantially constant fluid permeability and at least one permeation enhancing material having an increasing fluid permeability and wherein the semipermeable material is formed to accept one or more inserts formed of the permeability enhancing material; 
 an osmotic composition that expands at a rate proportional to the rate at which fluid passes through the rate controlling member, the osmotic composition located inside the reservoir; and 
 an active agent formulation in fluid communication with the delivery orifice. 
 
     
     
       2. The osmotic pump of  claim 1 , wherein the rate controlling member has a fluid permeability rate that increases with time. 
     
     
       3. The osmotic pump of  claim 1 , wherein the one or more inserts of permeability enhancing material are sized and shaped to be received within a hollow interior portion formed within the semipermeable membrane. 
     
     
       4. The osmotic pump of  claim 1 , wherein the semipermeable material is selected from the group consisting of polyester elastomers, cellulose esters, cellulose ethers and cellulose ester-ethers, water flux enhanced ethylene-vinyl acetate copolymers, and mixtures thereof. 
     
     
       5. The osmotic pump of  claim 1 , wherein the permeability enhancing material is selected from the group consisting of osmotic agents, water-soluble materials, water degradable materials, and biodegradable materials. 
     
     
       6. The osmotic pump of  claim 1 , wherein the permeability enhancing material is selected from the group consisting of magnesium sulfate, magnesium chloride, sodium sulfate, sodium chloride, lithium sulfate, sodium phosphate, potassium phosphate, d-mannitol, sorbitol, inositol, urea, magnesium succinate, tartaric acid, raffinose, monosaccharides, oligosaccharides, polysaccharides, and mixtures thereof. 
     
     
       7. The osmotic pump of  claim 1 , wherein the permeability enhancing material is selected from the group of polymer materials consisting of biodegradable polylactides, polyglycolides, polycaprolactones, polyanhydrides, polyorthoester, polydioanones, polyacetals, polyketals, polycarbonates, polyphosphoesters, polyorthocarbonate, polyphosphazenes, polyurethanes, and copolymers of lactide and glycolide. 
     
     
       8. The osmotic pump of  claim 1 , wherein the permeability enhancing material comprises a polyurethane having a hydrolysable soft segment. 
     
     
       9. The osmotic pump of  claim 8 , wherein the hydrolysable soft segment is selected from the group consisting of a polycaprolactone, a copolymer of polycaprolactone with a polylactic acid, a copolymer of polycaprolactone with a polyglycolic acid, and a mixture of polycaprol actone with polyethylene glycol. 
     
     
       10. The osmotic pump of  claim 1 , wherein the permeability enhancing material comprises a matrix material having a porous material and a degradable material. 
     
     
       11. The osmotic pump of  claim 1 , further comprising a movable piston located between the osmotic composition and the active agent formulation. 
     
     
       12. The osmotic pump of  claim 1 , wherein the osmotic composition is selected from the group consisting of an osmotic agent and an osmotic polymer. 
     
     
       13. The osmotic pump of  claim 1 , wherein the osmotic composition is selected from the group consisting of osmotic tablets, powdered material, and flowable gel material. 
     
     
       14. The osmotic pump of  claim 1 , further comprising a filler distributed within or around the osmotic composition. 
     
     
       15. The osmotic pump of  claim 1 , wherein at least a portion of the rate controlling member is interference fit into the opening at the first end of the reservoir. 
     
     
       16. The osmotic pump of  claim 1 , wherein at least a portion of the rate controlling member is adhered into the opening at the first end of the reservoir. 
     
     
       17. The osmotic pump of  claim 1 , wherein a portion of the rate controlling member is initially filled by a plug formed of a material that degrades or erodes when exposed to the intended environment of operation.